Synthesis and biological evaluation of chromone carboxamides as calpain inhibitors

Lee, Kwang Seob; Seo, Seon Hee; Lee, Yong Ha; Kim, Ha Dong; Son, Miwon; Chung, Bong Young; Lee, Jae Yeol; Jin, Changbae; Lee, Yong Sup

doi:10.1016/j.bmcl.2005.03.095

Cited by 46 publications

(17 citation statements)

References 23 publications

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“…Experiments performed in hippocampal neurons suggest that calpains are involved in the cell death mechanisms triggered by activation of AMPA/kainate receptors (32). In this neurotoxic model caspases have been shown to be involved in excitotoxic damage caused by glutamate receptor activation, but they do not appear to be involved in the activation of KA receptors (32,42).…”

Section: Calpain Activation In Other Pathological Conditionsmentioning

confidence: 85%

“…This transcription factor is involved in the regulation of neuronal cell death by activating p53 and p73, decreasing the pro-survival action of the caspase pathway's NF êB activation, and by synthesizing DNA. The most recent apoptotic pathway that was shown to be governed by calpains is the activation of cyclin-dependent kinase 5 (cdk5) by cleaving cdk5 /p35 to cdk5/p25 (2,19,32,38,39) (Fig. 2).…”

Section: Role Of Calpain Activation In Neuronal Cell Deathmentioning

confidence: 99%

“…Instead, cdk5 activity requires association with one of the two brain-specific regulatory subunits called p35 and p39. Unlike other cyclin-dependent kinases, cdk5 is not involved in cell cycle regulation and is localized in the central nervous system (24,27,28,32). Using an antisense strategy, Alvarez et al were first to describe the role of cdk5 in an experimental model of AD (2).…”

Section: Alzheimer's Diseasementioning

confidence: 99%

“…It is well known that calcium ions are intracellular messengers involved in the regulation of important physiological functions, including synaptic activity, membrane excitability, exocytosis, and enzyme activation (32,80). Although neurons possess mechanisms to regulate intracellular calcium levels, a deregulation or dramatic increase in the cytoplasmatic levels of calcium is the first indicator of neuronal cell death (4,49,56,63).…”

Section: Introductionmentioning

confidence: 99%

“…Although neurons possess mechanisms to regulate intracellular calcium levels, a deregulation or dramatic increase in the cytoplasmatic levels of calcium is the first indicator of neuronal cell death (4,49,56,63). Thus, calcium overload could significantly contribute to neuronal injury through activation of several enzymes such as calpains and phospholipase A 2 , as well as mitochondrial alterations (3,5,32,33,46). It is widely known that mitochondria have been implicated in neuronal cell death through the release of key proteins such as cytochrome c (Cyt c), the second mitochondria derived activator of caspase (Smac, also known as DIABLO), and apoptosis-inducing factor (AIF) (15,17,25,33).…”

Section: Introductionmentioning

confidence: 99%

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Involvement of Calpain Activation in Neurodegenerative Processes

et al. 2006

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One of the challenges in the coming years will be to better understand the mechanisms of neuronal cell death with the objective of developing adequate drugs for the treatment of neurodegenerative disorders. Caspases and calpains are among the best-characterized cysteine proteases activated in brain disorders. Likewise, during the last decade, extensive research revealed that the deregulation of calpains activity is a key cytotoxic event in a variety of neurodegenerative disorders. Moreover, interest in the role of calpain in neurodegenerative processes is growing due to implication of the involvement of cdk5 in neurodegenerative diseases. Since calpain inhibitors appear to not only protect brain tissue from ischemia, but also to prevent neurotoxicity caused by such neurotoxins as â-amyloid or 3-nitropropionic acid, the currently available data suggest that calpain and cdk5 play a key role in neuronal cell death. It seems clear that the inappropriate activation of cysteine proteases occurs not only during neuronal cell death, but may also contribute to brain pathology in ischemia and traumatic brain disorders. Pharmacological modulation of calpain activation may, therefore, be useful in the treatment of neurodegenerative disorders. It is possible, although difficult, to develop synthetic inhibitors of cysteine proteases, specifically calpains. The inhibition of calpain activation has recently emerged as a potential therapeutic target for the treatment of neurodegenerative diseases. 135

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Section: Calpain Activation In Other Pathological Conditionsmentioning

confidence: 85%

Section: Role Of Calpain Activation In Neuronal Cell Deathmentioning

confidence: 99%

Section: Alzheimer's Diseasementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Involvement of Calpain Activation in Neurodegenerative Processes

et al. 2006

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Stroke Therapy

Nantermet

Shalen

Shankar

et al. 2010

Burger's Medicinal Chemistry and Drug Discovery

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Metalated Chromene and Chromone Complexes: pH Switchable Metal–Carbon Bonding Interaction, Photo‐triggerable Chromone Delivery Application, and Antioxidative Activity

Chung

Yeung

et al. 2017

Chemistry A European J

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The two families of Ru -chromene and -chromone complexes isolated in this work represent the first examples of metalated chromene and chromone complexes synthesized through transition-metal-mediated cyclization of phenol-tethered ynone. These unprecedented metalated heterocyclic compounds exhibit remarkable features, such as pH-switchable metal-carbon bonding interactions, photo-triggerable release of organic chromone upon visible-light irradiation, and superior antioxidative property to their organic analogue (1,4-benzopyrone). These findings not only offer mechanistic insights into metal-induced activation of functionalized alkynes, but also add a new dimension to rational design of antioxidants and photo-responsive drug delivery systems.

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Synthesis and biological evaluation of chromone carboxamides as calpain inhibitors

Cited by 46 publications

References 23 publications

Involvement of Calpain Activation in Neurodegenerative Processes

Involvement of Calpain Activation in Neurodegenerative Processes

Stroke Therapy

Metalated Chromene and Chromone Complexes: pH Switchable Metal–Carbon Bonding Interaction, Photo‐triggerable Chromone Delivery Application, and Antioxidative Activity

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